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Differentiation of Cytochrome P450-Mediated from Non-CYP-Mediated Metabolism: Aldehyde Oxidase and Xanthine Oxidoreductase

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Book cover Cytochrome P450

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Aldehyde oxidase and xanthine oxidoreductase are part of the molybdo-flavo family of enzymes. They have become increasingly relevant in drug discovery as medicinal chemistry strategies evolve to reduce cytochrome P450 (CYP) related drug metabolism. Consequently, there is a need for a differentiation strategy for test compounds to be characterized from those of CYP and molybdenum-containing hydroxylases. Herein, general procedures to identify activity and differentiate the fraction metabolized by aldehyde oxidase and xanthine oxidoreductase from that of the family of CYP enzymes are described. Additionally, identifying structural features that lend themselves to aldehyde oxidase and xanthine oxidoreductase metabolism, tissue fractions appropriate to measure activities of these enzymes, specific cofactors to add or omit, specific inhibitors, kinetic idiosyncrasies, and confirmatory studies are detailed.

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Authors and Affiliations

  1. Takeda Pharmaceuticals, San Diego, CA, USA

    Kirk D. Kozminski & Michael A. Zientek

Authors
  1. Kirk D. Kozminski
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  2. Michael A. Zientek
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Corresponding author

Correspondence to Kirk D. Kozminski .

Editor information

Editors and Affiliations

  1. Genentech Inc., South San Francisco, CA, USA

    Zhengyin Yan

  2. Blue Bell, PA, USA

    Gary W. Caldwell

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© 2021 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Kozminski, K.D., Zientek, M.A. (2021). Differentiation of Cytochrome P450-Mediated from Non-CYP-Mediated Metabolism: Aldehyde Oxidase and Xanthine Oxidoreductase. In: Yan, Z., Caldwell, G.W. (eds) Cytochrome P450. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1542-3_17

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  • DOI: https://doi.org/10.1007/978-1-0716-1542-3_17

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1541-6

  • Online ISBN: 978-1-0716-1542-3

  • eBook Packages: Springer Protocols

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